Neuromodulation is important for behavioral plasticity. The overall goal of this study is to explore the molecular and biochemical nature of this link. Novel dopamine and octopamine receptors of Drosophila have been isolated and shown to have highly enriched expression in the mushroom bodies, a brain structure indispensable for olfactory learning. The receptors produce increases in cAMP and intracellular Ca2+, key mediators of signal transduction pathways crucial for synaptic plasticity. Using recently isolated receptor mutants, the studies will focus on addressing three fundamental questions. 1) Do the receptors play a role in associative learning? 2) Do the receptor mutants fail at all types of learning or is there a selective deficit? 3) Which effector systems, cAMP and/or Ca2+, are responsible for any behavioral deficits observed? Given the diversity and complexity of behavior, comparative studies of the receptor mutants in behavioral paradigms should help dissect the elaborate physiological processes underlying behavioral plasticity. These studies may help to understand the roles for biogenic amines in human diseases, such as schizophrenia, and the actions of biogenic amine receptors in cognition.